Ttyh1, a Ca2+-Binding Protein Localized to the Endoplasmic Reticulum, Is Required for Early Embryonic Development

被引:27
|
作者
Kumada, Tomohiro [1 ]
Yamanaka, Yasunari [1 ]
Kitano, Ayumi [1 ]
Shibata, Minoru [1 ]
Awaya, Tomonari [1 ]
Kato, Takeo [1 ]
Okawa, Katsuya [2 ]
Abe, Takaya [3 ]
Oshima, Naoko [3 ]
Nakahata, Tatsutoshi [1 ]
Heike, Toshio [1 ]
机构
[1] Kyoto Univ, Dept Pediat, Grad Sch Med, Kyoto, Japan
[2] Kyoto Univ, Grad Sch Med, Biomol Characterizat Unit, Kyoto, Japan
[3] RIKEN, Lab Anim Resources & Genet Engn, Ctr Dev Biol, Wako, Saitama, Japan
基金
日本学术振兴会;
关键词
Ttyh1; endoplasmic reticulum; early lethality; Ca2+-binding; CELL-PROLIFERATION; CALCIUM;
D O I
10.1002/dvdy.22348
中图分类号
R602 [外科病理学、解剖学]; R32 [人体形态学];
学科分类号
100101 ;
摘要
Using comprehensive genetic studies on neuronal stem/progenitors cells through genome-wide screening with oligonucleotide arrays, we identified an endoplasmic reticulum (ER) -resident protein, Tweety homologue 1 (ttyh1). Ttyh1 encodes a glycosylated protein composed of five predicted transmembrane segments and a C-terminus that is enriched in negatively charged residues capable of Ca2+ binding. Ttyh1-containing membranes changed to segmented tubuloreticular structures during mitosis, suggesting that the ER-containing Ttyh1 could be responsible for Ca2+ sequestration and Ca2+ concentration regulation during mitosis. Ttyh1 inactivation in mice resulted in early embryonic lethality before organization of the nervous system, revealing that ttyh1 is essential in murine embryonic development. Our findings indicate that Ttyh1 plays an indispensable role during mitosis in early embryogenesis, possibly by maintaining Ca2+ homeostasis in the ER. Developmental Dynamics 239:2233-2245, 2010. (C) 2010 Wiley-Liss, Inc.
引用
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页码:2233 / 2245
页数:13
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